Statin Skepticism



Statins, drugs that lower cholesterol, are among the most widely prescribed medications in America. For those who have experienced an acute cardiac event, such as a heart attack, statin treatment may be warranted to prevent a second event. This is called secondary prevention. However, the data is weak that statins are beneficial for primary prevention i.e. preventing cardiac events in those who have never had a heart attack. And yet, they are handed out like candy on Halloween. But now some experts are questioning which is healthier, the statin or the Halloween candy!?!


A review article published in the Expert Review of Clinical Pharmacology by Harumi Okuyama and colleagues entitled, “Statins Stimulate Atherosclerosis and Heart Failure,” lays out nicely three main mechanisms by which statins might actually be toxic to your body!


  1. Statins decrease energy production in your heart muscle cells. Your heart muscle cells need energy in the form of ATP, the energy currency of the cell, to contract and function properly. The generation of ATP depends on your mitochondria, and specifically a set of proteins and other molecules inside your mitochondria that make up what is called the electron transport chain. Two important components of the energy producing electron transport chain are called “Coenzyme Q” and Heme A.” Statins inhibit the synthesis of “Coenzyme Q” and Heme A,” leading to a decrease in ATP production, impairment of heart muscle cells, and, possibly, the onset of heart failure.
  2. Statins inhibit important stress-fighting “selenoproteins.” Some protein enzymes contain the element selenium and are, therefore, named selenoproteins. Two examples of selenoproteins are glutathione (GSH) peroxidase and thioredoxin reductase. These names aren’t particularly important. What is important is to understand that these proteins combat the oxidative stress that is toxic to cells and their mitochondria. Unfortunately, statins inhibit the synthesis of these selenoproteins, as well as of other anti-oxidant proteins like SOD and catalase. In this way, statins can increase oxidative stress and further damage heart muscle cells and contribute to the onset of heart failure.
  3. Statins inhibit the synthesis of Vitamin K2. We all know that calcium is good for our bones, and many of us know that we need Vitamin D to help us absorb calcium from our diets; however, calcium and Vitamin D actually make up a nutritional triad along with Vitamin K2. While Vitamin D helps us absorb dietary calcium, Vitamin K2 activates proteins (matrix Gla and osteocalcin) that help transport that calcium from the blood into our bones! Since statins inhibit Vitamin K2 synthesis, they can prevent this process from occurring. Not only does this mean less calcium for bones, but the calcium that is then left in the blood can deposit into arterial plaques, causing the dangerous calcification of plaques that contributes to heart disease.



The diagram summarizes the three mechanisms detailed above and also points to some other troubling disease-related implications of these mechanisms. First, statins inhibit “Heme A” synthesis (mechanism 1). “Heme A” is a critical component of cytochrome c oxidase in the electron transport chain. Since cytochrome c oxidase (a.k.a. complex IV) is known to be impaired in Alzheimer’s disease, one could question if statins could increase a person’s risk for developing dementia. Second, selenoproteins are involved in several steps of glucose metabolism, suggesting that treatment with statins could cause diabetes through mechanism 2. In fact, this is more than speculation. Statins are known to increase a person’s risk of developing type II diabetes. Third, iodothyronine deiodinases, enzymes important in the activation of thyroid hormone, are a selenoproteins. This means that statins could also contribute to hypothyroidism. And fourth, although perhaps this was already implied, by inhibiting the synthesis of Vitamin K2 (mechanism 3), statins could contribute to osteoporosis.


To be clear, with the exception of the diabetes connection, the above comments are purely SPECULATIVE HYPOTHESES that may only apply to some people and are not to be construed, in any way, as medical advice. In fact, statins have even been associated with DECREASED risk of dementia and osteoporosis, in some populations. The point I’m trying to make is not that statins are bad. My objective with this piece is simply to play devil’s advocate against a class of drugs that perhaps we prescribe too widely without weighing the potential cons. 


Good science, and good medicine, are about being cautiously skeptical. 


Below are some data from the review, for those who want a peak.


Nicholas Norwitz

*The views and opinions expressed herein are those of the author and do not necessarily reflect the views of, its affiliates, or its employees.